Processes that utilize a liquid or solvent are routinely used in the preparation of solid pharmaceutical compositions. Recently it has been discovered that some pharmaceutical compositions made by a spray-drying process can enhance the aqueous concentration and bioavailability of low-solubility drugs. See, for example, commonly owned EP 0 901 786 A2, which discloses forming solid amorphous dispersions of low-solubility drugs and the cellulosic polymer hydroxypropyl methyl cellulose acetate succinate (HPMCAS) by spray-drying, and commonly owned WO 03/000238 A1, which discloses forming adsorbates of a low-solubility drug onto high surface area substrates using a spray-drying process. Such dispersions and adsorbates contain non-crystalline drug in the form of drug-containing particles, and exhibit concentration enhancement of the drug relative to crystalline drug alone.
Pharmaceutical compositions made by solvent processing often contain a low concentration of the solvent used to form the composition immediately after removal from the apparatus in which they are made. This “residual solvent” may be at a concentration of about 2 to 10 wt %. Since a desirable final residual solvent content in such drug-containing particles is on the order of 1 wt % or less for purposes of drug stability and purity, secondary drying following spray drying is often required. Another characteristic of such particles formed by spray drying is that they tend to be small (less than 500 μm in diameter) and have low density (bulk specific volumes greater than about 1.5 mL/g).
Various dryers have been suggested for removing residual solvent from pharmaceutical compositions, including tray dryers, fluidized-bed dryers, microwave dryers, belt dryers, and rotary dryers. These dryers typically contact the pharmaceutical composition with warm or hot air or an inert gas. However, while such dryers can be effective and are commercially available, all have drawbacks. For example, tray dryers require a substantial amount of time to reduce the solvent content to acceptable levels and are prone to producing non-uniform dried product. Rotary dryers, which consist of a rotating drying chamber, are typically used for drying small amounts of material and require a substantial amount of time to remove the residual solvent to an acceptable level.
Thus, there is a need in the art for a relatively quick and energy-efficient secondary drying process for producing drug-containing particles with acceptable residual solvent content.